Recently confirmed apoptosis-inducing lead compounds isolated from marine sponge of potential relevance in cancer treatment

Despite intense efforts to develop non-cytotoxic anticancer treatments, effective agents are still not available. Therefore, novel apoptosis-inducing drug leads that may be developed into effective targeted cancer therapies are of interest to the cancer research community. Targeted cancer therapies affect specific aberrant apoptotic pathways that characterize different cancer types and, for this reason, it is a more desirable type of therapy than chemotherapy or radiotherapy, as it is less harmful to normal cells. In this regard, marine sponge derived metabolites that induce apoptosis continue to be a promising source of new drug leads for cancer treatments. A PubMed query from 01/01/2005 to 31/01/2011 combined with hand-curation of the retrieved articles allowed for the identification of 39 recently confirmed apoptosis-inducing anticancer lead compounds isolated from the marine sponge that are selectively discussed in this review.     

Distal aortic aneurysm presumed to be secondary to an infected umbilical artery in a foal

Abstract

CASE HISTORY:?A 3-month-old female Warmblood foal was presented after displaying signs of colic with pyrexia for 5 days.

CLINICAL AND PATHOLOGICAL FINDINGS:?The foal continued to show signs of colic, frequently passed urine, and was pyrexic with an elevated white blood cell count. The umbilical stalk was thickened but there was no evidence of purulent material. Exploratory laparotomy revealed an enlarged left umbilical artery remnant tightly adhered to the bladder wall. The left umbilical artery continued to an aneurysm involving the distal aorta. The foal was subject to euthanasia and post-mortem examination confirmed a spherical aortic aneurysm, in the dorsal midline caudal to the kidneys that contained a large thrombus. Histopathological examination revealed inflammation and necrosis of the tunica intima and tunica media of the left umbilical artery with suppuration and bacterial colonies evident in the periarterial tissues.

DIAGNOSIS:?Infected aortic aneurysm presumably caused by an umbilical artery infection.

CLINICAL RELEVANCE:?A previously undetected umbilical infection appears to have resulted in an unusual delayed complication causing signs of colic in a foal. Veterinarians should be aware of this condition, and the possibility that it may be a cause of signs of colic in foals. Diagnosis based on ultrasonography should be possible, but may require sedation, visceral analgesia and careful examination.     

How economic are the farming units of Leliefontein,Namaqualand?

Nomadic pastoralism has been practised in Leliefontein for centuries. In 1984, the area was formally divided into 47 so‐called ‘economic units’ on the assumption that this agricultural approach would (a) promote development in the region and (b) introduce conservation management to these areas. The communal land tenure system was effectively abolished. We relate potential income from livestock farming in the region to costs of production and show that most of the 47 farming units of Leliefontein are, in fact, not economic farming units. Furthermore, there is little evidence to indicate that it has been the communal system per se that has been responsible for land degradation in the area. We point out that the change in land tenure, was based on technical considerations only, that the hidden costs were not adequately investigated and that the social ramifications were ignored.     

Surgical repair and reconstruction of a nasal fistula following intra-lesional formalin injection

A 6-year-old Cleveland Bay mare was referred to the University of Liverpool Equine Hospital for repair of an iatrogenic nasocutaneous fistula. The fistula had developed following attempted ablation of an epidermal inclusion cyst located in the right nasal diverticulum with intra-lesional formalin 6 weeks previously. Subsequent tissue necrosis resulted in the formation of a full-thickness defect in the overlying tissues and the creation of a 5 × 5 cm nasocutaneous fistula. Surgical management consisted of initial debridement of the fistula and use of a commercial dermal regeneration mesh to bridge the defect, acting as a tissue scaffold. The levator labii superioris muscle was utilised to cover the scaffold by transecting it close to its proximal origin and reflecting it rostrally. Finally, a transposition skin flap was created adjacent to the site and was rotated to cover the defect. The mare made an excellent recovery, and follow-up confirmed complete healing of the surgical site with an excellent cosmetic outcome.     

The comparison of equine articular cartilage progenitor cells and bone marrow-derived stromal cells as potential cell sources for cartilage repair in the horse

A chondrocyte progenitor population isolated from the surface zone of articular cartilage presents a promising cell source for cell-based cartilage repair. In this study, equine articular cartilage progenitor cells (ACPCs) and equine bone marrow-derived stromal cells (BMSCs) were compared as potential cell sources for repair. Clonally derived BMSCs and ACPCs demonstrated expression of the cell fate selector gene, Notch-1, and the putative stem cell markers STRO-1, CD90 and CD166. Chondrogenic induction revealed positive labelling for collagen type II and aggrecan. Collagen type X was not detected in ACPC pellets but was observed in all BMSC pellets. In addition, it was observed that BMSCs labelled for Runx2 and matrilin-1 antibodies, whereas ACPC labelling was significantly less or absent. For both cell types, osteogenic induction revealed positive von Kossa staining in addition to positive labelling for osteocalcin. Adipogenic induction revealed a positive result via oil red O staining in both cell types. ACPCs and BMSCs have demonstrated functional equivalence in their multipotent differentiation capacity. Chondrogenic induction of BMSCs resulted in a hypertrophic cartilage (endochondral) phenotype, which can limit cartilage repair as the tissue can undergo mineralisation. ACPCs may therefore be considered superior to BMSCs in producing cartilage capable of functional repair.     

Molecular mechanism of the suppression of larval skeleton by polycyclic aromatic hydrocarbons in early development of sea urchin <Emphasis Type="Italic">Hemicentrotus pulcherrimus</Emphasis>

Polycyclic aromatic hydrocarbons including benz[a]anthracene (BaA) are priority pollutants in the aquatic environment. Our previous study revealed that BaA and its metabolite, 4-monohydroxylated BaA (4-OHBaA) inhibit larval skeletogenesis in the sea urchin Hemicentrotus pulcherrimus. Here we report studies to elucidate the target of skeletogenesis inhibition elicited by BaA and 4-OHBaA. First, we performed an in vitro experiment using isolated micromeres which give rise to the larval skeletogenic mesenchyme. However, skeletogenesis was not repressed by BaA and 4-OHBaA, implying that these chemicals indirectly influence on the formation of larval skeleton. Next, we analyzed their influence in vivo using embryos. Vascular endothelial growth factor (VEGF) that is expressed in the ectoderm and induces spicule formation was inhibited by BaA and 4-OHBaA treatment. These chemicals also suppressed the expression of the heparan sulfate 6-O endosulfatase (Sulf) known as a VEGF signaling modulator. We, therefore, propose that BaA and 4-OHBaA effects on larval skeletogenesis via VEGF signaling. Furthermore, we showed that the expression of Endo16 mRNA, an endodermal marker, decreased after BaA and 4-OHBaA exposure, suggesting that these chemicals affect endodermal function together with skeletogenesis. This study demonstrates that BaA and 4-OHBaA exert multiple detrimental effects on the development of H. pulcherrimus.